Expression of the multidrug resistance protein MDR1/P-glycoprotein in acute leukemia patients

ABSTRACT

Therapeutic resistance is a major obstacle in the treatment of acute leukemia which has been closely associated with treatment failure. One of the mechanisms of drug resistance involves over expression of the multidrug resistance gene product, P glycoprotein [MDR1/pgp]. In this study the extent of MDR1/Pgp expression in patients suffering from acute leukemia and its possible prognostic role were evaluated. Twenty -five leukemia patients with mean age of 22.3 +/- 19.6 years were evaluated for percentage cells expressing MDR1/Pgp and mean fluorescence index reflecting intensity of expression using flow cytometry. Evaluation was performed at diagnosis and 21 days after induction chemotherapy to assess possible prognostic role of Pgp expression. 10 age matched control subjects were enrolled in the study. At diagnosis, mean percentage of cells expressing MDR1/Pgp were significantly higher in acute leukemia patients compared to controls [P < 0.05]. Further significant elevation of both percentage cells expressing Pgp and Mil was noted comparing patient results before and after induction chemotherapy [P < 0.05 for each]. On comparing percentage of cells expressing Pgp and MF1 in responders and non responders to standard therapy protocols, there was no significant difference before initiation of therapy, while after induction chemotherapy both parameters showed a statistically significant higher values in non-responders compared to responders [P < 0.05 for each]. Thus, increased expression of MDR1/Pgp is noted in acute leukemia cases with more evident over-expression after use of chemotherapy. Enhanced Pgp expression can affect the response of acute leukemia patients to chemotherapy opening the way for a possible role of MDR1 modulating drugs